DNAscope, a germline variant-calling pipeline from San Jose-based analytics firm Sentieon, achieved superior SNP and indel accuracy as compared to other standard datasets, according to a recent preprint from the company. The study authors coupled DNAscope with MGI Standard MPS chemistry, training a new DNAscope model for the MGI DNBSEQ-G400* sequencing platform.

The highly accurate Genome Analysis Toolkit (GATK) HaplotypeCaller is the industry-standard small variant caller. However, existing short-read variant callers, including HaplotypeCaller, have imperfect matching to high-confidence variant calls, especially across clinically relevant complex genomic regions. Improving accuracy at these sites is increasingly important, the study authors said, as next-generation sequencing data sees greater use in the clinic.

Sentieon’s DNAscope combines the established methods of haplotype-based variant callers with machine learning for greater accuracy. The system improves on active region detection and local assembly for higher levels of sensitivity and robustness, especially across high-complexity regions. DNAscope outputs candidate variants along with informative annotations, and candidates are transferred to a machine-learning model for variant genotyping.

DNAscope MGI Model v0.5 Training on DNBSEQ-G400 Sequencing Platform

The researchers developed a DNAscope MGI model to analyze the accuracy of current PE150 WGS reads generated on MGI’s DNBSEQ-G400 medium throughput benchtop sequencer, which the researchers say was selected for its comprehensiveness and flexibility.

Overview of model training and benchmarking pipeline.

The platform, combined with the trained DNAscope model, delivered higher accuracy than previously published benchmarks and other mainstream platforms. It also exhibited faster processing speed, while enabling fewer false negative and false positive variant calls as Sentieon’s DNAscope was able to model systematic error patterns more accurately.

“MGI provides high-quality sequencing products, giving the genomics community more choices in sequencing platforms. We at Sentieon are very happy to optimize DNAscope for MGI sequencers and jointly launch this secondary analysis solution for MGI's customers,” said Jun Ye, CEO of Sentieon. “This optimized pipeline helps MGI and their customers achieve high-performance computing efficiency, ease of use, and high accuracy. We look forward to continued collaborations in the future to provide high-quality solutions for the genomics industry.”

With high accuracy and low cost, DNBSEQ-G400 may make high-performance sequencing projects more accessible to researchers and clinicians, especially those working on human diseases and population diversity using large sample sets. Paired with Sentieon’s DNAscope, the system can provide improved variant calling, including in complex genomic regions that are clinically relevant, potentially facilitating more relevant clinical discoveries and treatment strategies.

The DNBSEQ-400 at ASHG.

As evidenced in this study, MGI’s DNBSEQ-G400 optimizes day-to-day sequencing while demonstrating higher SNP and indel detection accuracy, according to Yongwei Zhang, MGI Americas CEO. The system has a daily data output of up to 1440 Gb with the option to run 1 or 2 flow cells using 2 types of flow cells (550M/reads vs 1800M/reads) and various read length options from SE50 to SE400 or PE300. Built with a new flow cell system and optimized optical and biochemical systems, DNBSEQ-G400 can flexibly and rapidly support a variety of different sequencing and data analysis in areas such as basic research, clinical research, forensics, and agriculture. With DNBSEQ-G400 released in the US in August and the first few instruments placed in customers’ labs within a week, Zhang said MGI exemplifies its commitment to local customers and partners to make sequencing more accurate, flexible, and affordable.

“MGI will compete based on our advantages of DNBSEQ technologies, complete workflow solutions including upstream sample/library prep automation, downstream BioIT solutions, excellent customer-focused services from our local team, and cost,” said Zhang. “Our target is to enable more and more customers to have choices of higher data quality and lower cost when they want to buy sequencing platforms. We will help them to do more cutting-edge research or offer more precise and affordable clinical tests.”

*Unless otherwise informed, StandardMPS and CoolMPS sequencing reagents, and sequencers for use with such reagents are not available in Germany, Spain, the UK, Hong Kong, Sweden, Belgium, Italy, Finland, Czech Republic, Switzerland, Portugal, Austria, and Romania. No purchase orders for StandardMPS products will be accepted in the USA until after January 1, 2023.